Wednesday, February 04, 2009

Prasugrel’s Magical Moment

We here at the IN VIVO Blog do love our advisory committee meetings. The anticipation. The preparation. The smell of the reams of briefing documents. And then, there’s the meeting itself, and we find ourselves waiting for that magical moment when the tide turns, and it becomes clear which way the committee is going to fall.

Sometimes a meeting can turn on a company presentation, like Biogen-Idec’s case for bringing Tysabri back on the market. Or the power of a single committee member, like the Cleveland Clinic’s Steven Nissen's tirade against attention deficit/hyperactivity disorder drugs. Or the strength of a risk management program, as with Pfizer’s inhaled insulin Exubera (the later commercial failure notwithstanding).

For Lilly and Daiichi Sankyo’s prasugrel, the key moment came from FDA itself.

Prasugrel didn’t come to the Cardiovascular & Renal Drug Products Advisory Committee without a few issues—all of which have been breathlessly reported by your friends here at the IN VIVO Blog. (Hey, when you have a company-saving drug that could replace a $5 billion blockbuster as the standard of care for platelet inhibition, that’s kind of an exciting story.)

Bleeding is a problem with prasugrel. As is the potential that prasugrel may stimulate the growth of existing malignant tumors. Drugs have been taken down for less, and when you put that profile in the context of the current drug safety environment, Lilly had a potential catastrophe on its hands.

We’ve already made the case for why we think FDA will approve prasugrel, but there was certainly still the potential that things could go terribly wrong at the advisory committee—especially given that one of the the drug’s biggest cheerleaders, cardiologist Steve Nissen, wasn’t there to wave his pom-poms and give a big shout-out to P-R-A-S-U-G-R-E-L.

Advisory committees are unpredictable. Anything can happen.

Prasugrel’s magical moment happened when Ellis Unger, the deputy director of FDA’s Cardiovascular and Renal Drugs Products Division, stepped up to the podium. Unger’s take on prasugrel’s risk-benefit profile—as well as his relaxed, often humorous, demeanor—put committee members at ease with the data. (You can read more about that in today’s issue of “The Pink Sheet” DAILY.)

FDA, Unger said, is confident that the bleeding risk is well-characterized and understood, and while there is a possibility that prasugrel stimulates tumor growth, it is not a carcinogen: “Does prasugrel cause cancer? We don’t think so.” Unger lauded Lilly for its presentation, and declared that prasugrel’s superiority over Plavix in preventing non-fatal myocardial infarction was “where the money is.”

But it wasn’t just what Unger said that was magical for prasugrel. It was the fact that he was the only one who said it. The decision to use Unger as the only formal FDA presenter on prasugrel (other senior officials were at the committee table) rather than a parade of statisticians and medical reviewers sent a clear, single message, and avoided the potential for muddying the waters. It was, in effect, the anti-Avandia.

FDA may be criticized for that later by those who believe that dissenting opinions from within the agency—like calls to severely limit prasugrel use—should have been heard. Those opinions were outlined in the briefing documents to the committee. But when it came time for the meeting itself, there was no question where FDA stood on the approvability of the NDA. And that made for a magical moment for prasugrel.

Sunrise photo courtsey of flickr user inanutshell.


Anonymous said...

Another reason may be that the one critic on the panel was mysteriously disinvited just one day before the meeting. Read all about it on CardioBrief.Org.

Anonymous said...

Once the official labeling is hammered out this may offer something" 3 fewer events per 1000 patients treated" with increased risk of a fatal bleed and some unclear connection to augmenting the progression of existing cancers. Do we have enough info to unleash this on the public, especially given Lilly's reputation of illegal label and exaggerated claims....I wonder?????